Structures of antimutagenic constituents in the peels of Citrus limon

Abstract

The methanolic extracts from the peels of Citrus limon were found to show antimutagenic effects against 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole, and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in the Ames test. From the methanolic extracts, four new coumarins (wakayamalimonol A-D) and a new furanocoumarin (wakayamalimonol E) were isolated together with fifteen known compounds. The absolute stereostructures of the new compounds were determined by chemical synthesis and the modified Mosher's method. Among the isolated constituents, coumarins, furanocoumarins, and limonoids showed antimutagenic effects in the Ames test. One of the major constituent, limonin, showed significant antimutagenic effects against mitomycinC and PhIP in the micronucleus test in vivo.

Isolation and structure elucidation of constituents of Citrus limon, Isodon japonicus, and Lansium domesticum as the cancer prevention agents

“…As a result, limonin (19) and lansionic acid (53) significantly decreased the frequency of micronucleated reticulocytes (MNRETs) treated with PhIP at 24 h and 48 h after the administration ( Fig. 4) [4,7].…”

“…Based on these studies, we searched for antimutagenic materials derived from foods. In the course of this study, we found using the Ames test that the methanolic (MeOH) extracts of C. limon [4,5], aerial parts of I. japonicus [6], and leaves of L. domesticum [7,8] showed antimutagenic effects against Trp-P-1 and PhIP. Therefore, we directed our efforts toward the isolation of their constituents and evaluation of the antimutagenic effects of the isolated constituents using the Ames test and in vivo micronucleus test.…”

“…The absolute stereochemistries of wakayamalimonol A (1) and B (2) were determined by the modified Mosher's method. In addition, for the identification of the chemical structure and bioassay, wakayamalimonols A (1), B (2) and limonoxime I (21) were synthesized (Scheme 1) [4,5].…”

“…The antibacterial (19) at low or high dose (0.02% or 0.04%, w/w) were given ad libitum. b Normal or sample feeds that included lansionic acid (53) at low or high dose (0.03% or 0.06%, w/w) were given ad libitum [4,8] activity of tested compounds against the S. typhimurium TA98 strain were tested using nutrient agar containing NaCl and all compounds showed weak [44: 23.2% inhibition at 400 nmol/plate, 54: 23.0% inhibition at 400 nmol/plate] or no (other compounds: < 5.0% inhibition at highest concentration in Table 1) antibacterial activities [4][5][6][7][8].…”

“…Antimutagenic activity of coumarins (1 and 2), limonoids(19 and 20), oxime and synthetic intermediates (21, 21a, and 21b), ent-kaurane diterpenoids(25, 26, 29, 30, and 33), and onoceranoid-type triterpenoids(44,(46)(47)(48)(49) 53, and 54) against Trp-P-1 (0.04 μg/plate) using the Ames test[4][5][6][7][8] a Inhibition % (Based on number of revertant colonies)…”